A resource for informing patients and caregivers about Multiple Sclerosis, its possible causes, effects, and treatments. Get the most current information on new developments, clinical trials and other important matters for anyone dealing with MS.

Wednesday, April 09, 2008

- Very high patient response rate to Sativex but statistical significance narrowly missed due to large, unexpected placebo response -- Ongoing Phase III trial in MS Spasticity on track and due to report in Q4 -- MS Spasticity trial has specific features designed to address placebo response -

This study is one of three Phase III trials for Sativex underway in 2008, each of which targets a distinct indication. The other European Phase III study in MS Spasticity, requested last year by the UK regulator in order to gain approval in this indication and which involves a different trial design, is on track to report later this year.

The primary efficacy endpoint in the study reported today was the proportion of patients whose pain reduced by at least 30% as measured on a 0-10 numerical rating scale (“responder analysis”). In this study, 50% of Sativex patients experienced a pain reduction of at least 30%, the second largest response rate seen in any Sativex study and amongst the largest seen for any pain treatment in the published literature. However, although the difference between the Sativex and placebo groups was clearly in favour of Sativex, it narrowly failed to reach statistical significance in this trial due to an unexpectedly large placebo response. Key secondary endpoints followed the same trend – in favour of Sativex versus placebo but not at a statistically significant level due to the very high placebo response.

The placebo response in the study reported today appears related to dosing design, whereby patients were able to self-administer the oral spray at will. This was intended to reflect as far as possible the “real world” use of Sativex whereby patients initially experiment with dosing of Sativex to find their optimum dose level and which, once established, is usually maintained thereafter. Analysis of the efficacy data at fixed dose levels demonstrates a highly significant difference between Sativex and placebo. However, a consequence of allowing patients to determine their own dose was that patients on placebo took significantly more doses than patients on Sativex, thus confounding the overall comparison. This validates the decision by GW last year to adopt a fixed target dose approach in both the ongoing studies of Sativex in MS Spasticity and Cancer Pain.

The safety profile of Sativex in this study is superior to that seen in previous studies. The withdrawal rate due to adverse events was 9% on Sativex vs 6% on placebo, the lowest seen in long duration Sativex studies. As in previous studies, the most common adverse event was dizziness. The rate of this adverse event was less than in previous studies (20% on Sativex vs 8% on placebo as compared with 32% vs 9%).

GW’s regulatory strategy is to file Sativex for approval in MS Spasticity in Europe and Cancer Pain in the United States. In Europe, regulatory discussions with the Medicines and Healthcare products Regulatory Agency (MHRA) have exclusively focused on MS Spasticity, a distinct indication supported by different clinical trials. Last year, the MHRA provided clear guidance on the additional clinical trial required for approval. As indicated above, this trial is on track and due to report later this year.

Dr Stephen Wright, R&D Director, said: “It is clear from the size of the response seen in this study that Sativex provides important improvements for these high need patients, even those that have failed to respond to all other pain treatments. It is frustrating that the extent of the placebo response has narrowly prevented the benefits seen on Sativex translating into a statistically significant outcome. The design of the MS Spasticity study due to report later this year is specifically focused on limiting the potential for placebo response and we expect the outcome of this trial and our other studies to confirm the benefits of Sativex.”

“MS Spasticity is a distinct indication supported by different clinical trials and the route to regulatory approval for Sativex as a treatment for this indication remains clear and unaffected by the data announced today.”

Dr Stuart Ratcliffe, Principal Investigator of the study and most recently Director, Pain Research Group, St Bartholomew’s and The Royal London Hospitals NHS Trust, added: “In seeking to replicate the real world usage of Sativex, where each patient finds his or her own optimum dose level, the design of this trial appears to have encouraged an abnormally high placebo response. However, this in no way should detract from the beneficial effects of Sativex seen in the study. Patients saw a marked improvement in their symptoms, a highly impressive effect since they are treatment resistant, and the study recorded the lowest drop-out rate, demonstrating the mild side effect profile of Sativex. My experience with Sativex continues to show that it is an extremely helpful medicine for these high need patients and I am confident that the ongoing trials which seek to address the placebo issue will demonstrate its value.”

Following a comprehensive review of this data, GW intends to carry out a further study in this patient population.

As at 31 March 2008, GW’s cash position stood at £18.5m.

There will be a conference call for analysts today at 8.30am BST. Analysts should contact Gemma Cross Brown at Financial Dynamics on +44 (0) 20 7831 3113 for details. There will be a live audio web cast of this call, which will be accessible on the press releases page in the investor relations section of the GW website (www.gwpharm.com). A recording of this call will be available on the GW website later today.

Enquiries:

GW Pharmaceuticals plc (Today) + 44 20 7831 3113

Dr Geoffrey Guy, Executive Chairman

(Thereafter) + 44 1980 557000

Justin Gover, Managing Director

Financial Dynamics

+ 44 20 7831 3113

David Yates / Ben Atwell

Notes to Editors

About GWGW was founded in 1998 and listed on the AiM, a market of the London Stock Exchange, in June 2001. Operating under license from the UK Home Office, the company researches and develops cannabinoid pharmaceutical products for patients who suffer from a range of serious ailments, in particular pain and other neurological symptoms. GW has assembled a team of over 100 scientists with extensive experience in developing both plant-based prescription pharmaceutical products and medicines containing controlled substances. GW occupies a world leading position in cannabinoids and has developed an extensive international network of the most prominent scientists in the field.

Sativex Phase III trial in MS Neuropathic Pain

This study focused on high need MS patients, who were already taking a range of currently available pain treatments, and yet still suffered severe pain, and who remained on such treatments during the course of the study. Improvements seen in this study therefore represent benefits over and above that which can be achieved with currently available medication. The study recruited patients in the UK, Canada, France, Spain and the Czech Republic and the duration of treatment in the study was 14 weeks.

GW has previously carried out a similar Phase III study with positive results, which was published in the peer-reviewed journal, Neurology. That study showed that Sativex was significantly superior to placebo in reducing pain (p=0.005) and sleep disturbance (p=0.003)1. In this previous study the placebo response was less than that seen in the study reported today.

Clinical & Regulatory Strategy for Sativex

The strategy for Sativex is focused on four specific therapeutic indications, each of which represents a distinct regulatory opportunity and each of which requires a distinct set of clinical efficacy data. These indications are as follows:

Each of these target indications is supported by existing positive Phase III data and will continue to be supplemented by further late stage trials over the next few years in order to supplement globally approvable regulatory packages and provide more data to support the marketing of the product post approval.

The lead indication for Sativex differs across different regions of the world. In the US, Cancer Pain is the chosen initial target. In Canada, MS Neuropathic Pain was the first approved indication, which has now been successfully followed by the approval in Cancer Pain. In Europe, the entry point for Sativex is MS, with MS Spasticity representing the nearest term approval possibility.

This clinical and regulatory programme is designed to provide multiple opportunities over the next few years to obtain approvals for Sativex across various indications in a number of territories.

About Me

Cary J. Polevoy holds M.B.A and undergraduate degrees from Michigan State University. An active investor since 1965, Mr. Polevoy began his investment career as a stockbroker. He has also been a NYSE Supervisory Securities Analyst, director of research, mutual fund portfolio manager, and CEO/CFO of various small companies.
He has worked for Merrill Lynch, EF Hutton, RAC Advisors, Quantum Fund, The Broe Companies, McKinley Medical, among others.
Diagnosed with multiple sclerosis in 1995, he is the author of the book, "MS TOOLKIT - THE PATIENTS' & CAREGIVERS' GUIDE TO MULTIPLE SCLEROSIS."
DISCLAIMER: While I used to be a securities analyst, portfolio manager and registered investment advisor, I no longer am. Any opinions expressed herein are personal opinions and are not expressed as recommendations, advice or bets.